Several studies in cognitive neuroscience have investigated the cognitive and affective modulation of pain. By contrast, fewer studies have focused on the social modulation of pain, despite a plethora of relevant clinical findings. Here we present the first review of experimental studies addressing how interpersonal factors, such as the presence, behavior, and spatial proximity of an observer, modulate pain. Based on a systematic literature search, we identified 26 studies on experimentally induced pain that manipulated different interpersonal variables and measured behavioral, physiological, and neural pain-related responses. We observed that the modulation of pain by interpersonal factors depended on (1) the degree to which the social partners were active or were perceived by the participants to possess possibility for action; (2) the degree to which participants could perceive the specific intentions of the social partners; (3) the type of pre-existing relationship between the social partner and the person in pain, and lastly, (4) individual differences in relating to others and coping styles. Based on these findings, we propose that the modulation of pain by social factors can be fruitfully understood in relation to a recent predictive coding model, the free energy framework, particularly as applied to interoception and social cognition. Specifically, we argue that interpersonal interactions during pain may function as social, predictive signals of contextual threat or safety and as such influence the salience of noxious stimuli. The perception of such interpersonal interactions may in turn depend on (a) prior beliefs about interpersonal relating and (b) the certainty or precision by which an interpersonal interaction may predict environmental threat or safety.